The invention relates to a preparation method for liquid chromatography mass spectrometry (LC-MS)-grade high-purity acetonitrile reagents. The method includes steps: subjecting raw acetonitrile to adsorption by the aid of adsorbents such as activated carbon and activated alumina, oxidizing for purification, rectifying, dehydrating and drying by the aid of a molecular sieve, filtering by the aid of a microfiltration membrane, filling nitrogen for packaging, and obtaining the LC-MS-grade high-purity acetonitrile reagents. By the method, the recovery rate is more than 98%, the yield is more than 95%, the purity reaches to more than 99.99%, application requirements of clients on scientific researches and subject studies of the LC-MS-grade high-purity acetonitrile reagents can be met, domestic vacancies of production of the LC-MS-grade high-purity acetonitrile reagents can be filled, dependency on foreign reagents is lowered, high-quality reagents are provided for growing wide application of LC-MS quantitative analysis in high-tech fields such as biomedical research and development, clinic, food safety detection, pesticide residue analysis, veterinary drug residues, legal examiners, criminal investigations, doping detection, drug testing, agriculture and environment protection.